Blood gas analysis



May 13, 1969 H. HILL BLOOD GAS ANALYSIS Filed Sept. 27, 1965 INVENTOR.

m J44 M WY'W' United States Patent O 3,443,904 BLOOD GAS ANALYSIS Harold I. Hill, Fairfield, 'Conn., assignor to The Perkin- Elmer Corporation, Norwalk, Conn., a corporation of New York Filed Sept. 27, 1965, Ser. No. 490,269 Int. Cl. G01n 33/16 US. Cl. 23-253 Claims ABSTRACT OF THE DISCLOSURE Apparatus for analyzing blood or other liquids for contained gases. A tubular reaction vial contains a support material, such as filter paper, which has wicking properties. The support material is impregnated with a reagent which, upon contact with the liquid sample, will release the gas of interest. The sample to be analyzed is injected into the vial and onto the support material, as by a syringe. A carrier gas is passed through the reaction vial and into a chromatograph where it is analyzed to reveal the presence of the released gas.

This invention relates to the analysis of gases in blood, and, more particularly, to the analysis of carbon dioxide in a blood or blood serum sample.

One of the most common analyses performed by a clinical laboratory is the determination of carbon dioxide in blood. Several procedures have been developed for making such an analysis. A laboratory procedure is described by Donald D. Van Slyke and John Plazin in a booklet entitled Micromanometric Analyses, published by The Williams and Wilkins Company. In addition, several instrumental methods have been proposed which utilize the Van Slyke reagents. Most carbon dioxide in blood is not free or in simple solution but is bound, most commonly in the form of bicarbonates, carbonates, and protein carbamates. In the instrumental techniques which have been proposed, blood or blood serum is mixed with the reagents required to release the carbon dioxide. The resultant gases are picked up by a carrier, such as helium, and passed through a gas chromatograph where the carbon dioxide is separated, detected, and reproduced as a peak on an electrical recorder. All of these approaches have certain disadvantages. One of the chief disadvantages arises from the necessity for thoroughly mixing the blood serum with the reagents. These reagents are normally in liquid form and, after the blood serum is introduced, the resultant liquid must be stirred or shaken to produce a complete reaction. This requires relatively expensive apparatus. It has also proved diflicult to achieve suitable contact between the carrier gas and reagent-serum solution to obtain a rapid and reproducible pickup of the released gases. In one approach for example, a vessel is employed which has a false bottom of fritted glass. Helium is passed through this fritted glass and into the liquid. The readout equipment is also expensive, requiring an electrical recorder. Furthermore, the technician normally transfers the recorded reading to a work sheet so that the recording itself becomes superfluous.

Accordingly, it is the primary object of the present invention to provide an improved method and apparatus for making blood gas analyses. Other objects are to provide apparatus which is simple, inexpensive and reliable; which does not require a special carrier gas supply; which does not require a high degree of skill on the part of a technician; and which produces a direct visual meter readout.

The manner in which the foregoing objects are achieved will be more apparent from the following description, the appended claims and the figures of the attached drawings, wherein:

FIG. 1 is a schematic illustration of the analysis portion of an instrument in accordance with this invention;

FIG. 2 is a front view of a disposable reaction vial forming a part of the instrument shown in FIG. 1, partially broken away to illustrate its internal construction;

FIG. 3 is an enlarged top view of the vial of FIG. 2;

FIG. 4 is a circuit diagram of the readout portion of the instrument of FIG. 1; and

FIG. 5 is a series of charts illustrating the operation of the invention.

The objects of this invention are achieved by means of a blood gas analyzer which comprisesa reaction vial enclosing a support material having wicking properties and supporting thereon a gas releasing agent. Means are provided for injecting a blood sample into the vial. A carrier gas is passed through the vial and detection means, which are responsive to the composition of the carrier gas, are provided to indicate the presence of released gas in the efiluent from the vial. As used herein, the term wicking means rapidly absorptive so as to quickly spread a liquid sample along the support material.

In the illustrated embodiment of this invention, the chemical reactions required for releasing carbon dioxide gas from blood serum take place within the reaction vial 10, which is illustrated most clearly in FIGS. 2 and 3. The reaction vial is a short glass or plastic tube which is open at both ends. The lower end of the tube contains a suitable desiccant 12 such as hydrated calcium sulphate held in place by a glass wool plug 14. The remainder of the tube is filled with a rolled filter paper support 1 6 which has been previously treated by soaking in a saturated solution of oxalic acid in methanol. The paper is then dried in an oven, rolled and inserted into the tube as illustrated. From FIG. 1 it will begnoted that the reaction vial 10 is inserted within a suitable holder 18 so that its upper end is connected to a carrier gas inlet line 20 and its lower end is connected to a gas outlet line 22. A thin rubber septum 24 is provided at the upper end of the vial, permitting the injection of blood serum by means of a hypodermic syringe 26.

One of the advantages of the present invention is that no separate source of carrier gas is required. This is due to the fact that air is employed as the carrier gas. Accordingly, the gas inlet line 20 is connected directly to an air inlet 28 by means of a two-way solenoid operated valve 30. The air inlet 28 and the gas outlet line 22 are connected to a three-way solenoid operated valve 32, which is connected to the inlet of a chromatographic column 34, packed with silica gel or other suitable substance. A thermistor thermal conductivity detector, including a reference cell 36 and a measuring cell 38, detects the carbon dioxide present in the column efiluent. The measuring cell 38 is connected directly to the column output end and the reference cell 36 is supplied with air through a suitable desiccant 40 such as hydrated calcium sulphate and a flow restrictor 42 which matches the resistance of column 34 and vial 10. The carrier and reference air inlets are in reasonably close proximity, thus cancelling out the efi'ects of any differences in the composition of room air. The column and measuring cells are contained within a heated and thermostated enclosure 43 at a temperature of 40 C. Air is caused to fiow through the entire apparatus by means of a vacuum pump 44 exhausting to a vent 46.

An analysis is made by setting valve 30 to its off position and setting valve 32 so as to interconnect the air inlet 28 with the chomatographic column 34. With the reaction vial 10 thus isolated from the remainder of the apparatus, a sample of blood serum is introduced by injection through the septum 24 with the syringe 26. The serum is deposited on the filter paper support 16 and, due to the absorbent nature of the filter paper and its large continuous exposed surface area, the sample is absorbed rapidly by the filter paper, contacting the layer of oxalic acid. The resultant reaction evolves the carbon dioxide from the serum.

After a short reaction time period, the valves 30, 32

are set to the positions illustrated in FIG. 1, causing air to be passed downwardly through the reaction vial and sweeeping the carbon dioxide into the chromatographic column 34. The column serves to integrate out any differences in sampling pulse width and decreases the variations in peak height with sampling variables. The resultant peak of carbon dioxide passes through the measuring cell 38 and on through the vacuum pump 44 and vent 46.

The readout portion of the invention may be best understood by referring to FIG. 4. The reference cell 36 includes a thermistor element 48 and the measuring cell 38 includes a thermistor element 50. Thermistor elements 48, 50 are included in a bridge circuit 52 and the output of the bridge is supplied -to a pulse amplifier 54. The output from pulse amplifier 54 is connected to two switches 56, 58. A storage capacitor 60 is connected across the switches and an electrometer tube 62 and a readout meter 64 are connected in series across the capacitor. The meter 64 is calibrated in millimoles of carbon dioxide per liter of blood or serum.

The operation of the circuit of FIG. 4 may be best understood by reference to FIG. 5. FIGS. d and 5e illustrate, respectively, the open and closed positions of switches 56 and 58. The shaded portions illustrate the periods of time during which each switch i in the closed position. FIG. 5a illustrates the electrical output from bridge circuit 52. FIG. 5b illustrates the electrical output from pulse amplifier 54, and FIG. 50 illustrates the charge across storage capacitor 60 and also illustrates the reading of the meter 64. A novel feature of this circuit is that the reading is held by the meter until cleared for the next analysis. This is illustrated by the first portion of FIG. 50 which indicates the existence of a preexisting reading on the meter 64, It will be noted that, during this period, switch 56 is open and switch 58 is closed. Prior to reading out the next analysis, the switch 56 is closed, as illustrated in FIG. 5d, thus shorting out capacitor 60 so that its charge and the meter reading both drop to zero as shown in FIG. 5c. As the gas sample begins to be swept from reaction vial through the column 34, switch 58 opens. The pulse from amplifier 54 is then applied to capacitor 60 by means of switch 56, causing the charge on the capacitor to build to a peak value as indicated in FIG. 50. Switch 56 opens and switch 58 closes, thereby holding the charge on the capacitor 60 and maintaining the reading on meter 64. The technician may then copy this reading onto the worksheet at his leisure.

It is believed that the many advantages of this invention will be fully apparent to those skilled in the art. It will be noted that the instrument is semiautomatic in nature and that the operator need only introduce a measured amount of serum into the unit and start a cycle timer. The remainder of the operation may be fully automatic, the meter holding the final value until it is read and cleared. The solenoids of valves 30, 32 and the switches 56, 58 may be operated by the cycle timer which may be a one revolution cam shaft. After a reading has been made, the reaction vial 10 is removed and discarded-a new vial being inserted for each reading. The vial itself encloses a single sheet of open mesh, coarse paper which will retain a relatively large amount of reagent while allowing the sample to spread rapidly. In addition, the paper is rolled about the longitudinal axis of the vial, reducing gas flow resistance to a minimum. It will be further noted that pulse techniques are employed to measure only the AC. component of the peak, Accordingly, base line drifts will be treated as DC. By measuring only the AC. component, slow baseline drifts are ignored and the instrument does not require frequent rezeroing,

It will also be apparent to those skilled in the art that variou modifications may be made in this invention without departing from its spirit and scope. For example, oxalic acid has been disclosed as a usable carbon dioxide releasing agent. However, any other suitable acidifying agent may also be employed. It will also be apparent that the reaction vial may be very inexpensively constructed of paper or plasticin much the same manner as a cigarette filter--and may not include a separate outer tube. Also, the invention may be employed to measure gases contained in other fluids. Accordingly, the foregoing description is to be construed as illustrative only, rather than limiting. This invention is limited only by the scope of the following claims.

What I claim as new and desire to secure by Letters Patent of the United States is:

l. A blood gas analyzer which comprises: a reaction vial enclosing a support material having wicking properties and impregnated with a reagent which, upon contact with a blood sample, will release a gas from said sample; means for injecting a blood sample into said vial; means for passing a carrier gas through said vial; and detection means responsive to the compositoin of carrier gas from said vial to indicate the presence of released gas entrained therein.

2. The analyzer of claim 1 wherein said support material is a sheet impregnated with said reagent.

3. The analyzer of claim 1 wherein said vial is a tube and wherein said support material is a rolled paper sheet.

4. The analyzer of claim 1 wherein said detection means comprises: a thermal conductivity bridge connected to produce an output signal; and indicator means responsive to said signal.

5. The analyzer of claim 1 wherein said detection means comprises: a chromatographic column connected to receive carrier gas from said vial; a thermal conductivity bridge at the output of said chromatographic column to produce an output signal peak; and indicator means responsive to the maximum amplitude of said peak.

6. A reactlon vial for releasing a gas from a liquid which comprises: a tubular rolled sheet support material having wicking properties; a reagent which, upon contact with a liquid sample, will release a gas from said sample, impregnated on said support material; and gas impermeable means enclosing said rolled support material and defining gas inlet and outlet means therein.

7. The vial of claim 6 wherein said support material is paper.

8. The vial of claim 6 wherein said reagent is an acid.

9. A reaction vial for releasing a gas from a liquid comprising: a tube; a rolled sheet support material having wicking properties enclosed within said tube; and a reagent impregnated on said support material which, upon contact with a liquid sample, will release a gas from said sample.

10. Apparatus for the analysis of gases in liquids which comprises: a disposable, tubular reaction vial having an input end and an output end and including a rolled support material having wicking properties and impregnated with a reagent which, upon contact with a liquid sample, will release a gas from said sample; means for injecting a liquid sample into the input end of said vial in contact with said support material; a chromatographic column and a measuring cell in series fluid flow relationship With the output end of said via]; a reference cell; means for admitting air into the input end of said vial; means for admitting air into said reference cell; means for venting said air from said reference and measuring cells; thermal conductivity responsive means in each of said reference and measuring cells for producing an electrical output proportional to the concentration of released gas eluted from said column; and means for visually indicating the value of said output.

References Cited UNITED STATES PATENTS 2,526,657 10/1950 Guyer 23288.92 2,946,665 7/1960 Skeggs.

MORRIS O, WOLK, Primary Examiner.

10 ELLIOTT A. KATZ, Assistant Examiner.

US. Cl. X.R. 23254 

